Phase noise of a microwave photonic channel: direct-current versus external electro-optic modulation

We characterize the phase noise of a microwave photonic channel, where a 10 GHz signal is carried by an intensity-modulated light beam over a short optical fiber, and detected. Two options are compared, (i) an electro-optic modulator (EOM), and (ii) the direct modulation of the laser current. The 1.55~$\mu$m laser and the detector are the same. The effect of experimental parameters is investigated, the main of which are the microwave power and the laser bias current. The main result is that the upper bound of the phase flicker is $-117$~dBrad$^2$ in the case of the EOM, limited by the background noise of the setup. In contrast, with direct modulation of the laser, the flicker is of $-114$ to $-100$~dBrad$^2$, depending on the laser bias current (50--90~mA), and the highest noise occurs at the lowest bias. Our results are of interest in communications, radar systems, instrumentation and metrology.Comment: 5 pages, 5 figures, 1 table, 43 bibliographic reference

A Reverse-Engineering Method for Powertrain Parameters Characterization Applied to a P2 Plug-In Hybrid Electric Vehicle with Automatic Transmission

Over the next decade, CO2 legislation will be more demanding and the automotive industry has seen in vehicle electrification a possible solution. This has led to an increasing need for advanced powertrain systems and systematic model-based control approaches, along with additional complexity. This represents a serious challenge for all the OEMs. This paper describes a novel reverse engineering methodology developed to estimate relevant powertrain data required for fuel consumption-oriented hybrid electric vehicle (HEV) modelling. The estimated quantities include high-voltage battery internal resistance, electric motor and transmission efficiency, gearshift thresholds, torque converter performance diagrams, engine fuel consumption map and front/rear hydraulic brake torque distribution. This activity provides a list of dedicated experimental tests, to be carried out on road or on a chassis dynamometer, aiming at powertrain characterization thanks to a suitable post-processing algorithm. In this regard, the methodology was applied on a P2 Diesel Plug-in HEV equipped with a 9-speed AT. Voltage and current sensors are used to measure the electrical power exchanged between battery and electric motor; a torque sensor on the propeller shaft measures the total torque coming out from the automatic transmission. The hydraulic pressures in the four brake calipers are measured and CAN data is logged. The results of the testing campaign are then presented and discussed. Functional models of powertrain subsystems are introduced and their parameters estimated using least square method. The good match between models and experimental data proved that the proposed methodology, if properly adapted to the specific layout, is a suitable tool for powertrain parameter estimation

Abscisic acid transport in human erythrocytes

Abscisic acid (ABA) is a plant hormone involved in the response to environmental stress. Recently, ABA has been shown to be present and active also in mammals, where it stimulates the functional activity of innate immune cells, of mesenchymal and hemopoietic stem cells, and insulin-releasing pancreatic \u3b2-cells. LANCL2, the ABA receptor in mammalian cells, is a peripheral membrane protein that localizes at the intracellular side of the plasma membrane. Here we investigated the mechanism enabling ABA transport across the plasmamembrane of human red blood cells (RBC). Both influx and efflux of [3H]ABA occur across intact RBC, as detected by radiometric and chromatographic methods. ABA binds specifically to Band 3 (the RBC anion transporter), as determined by labeling of RBC membranes with biotinylated ABA. Proteoliposomes reconstituted with human purified Band 3 transport [3H]ABA and [35S]sulfate, and ABA transport is sensitive to the specific Band 3 inhibitor 4,4\u2032-diisothiocyanostilbene-2,2\u2032-disulfonic acid. Once inside RBC, ABA stimulates ATP release through the LANCL2-mediated activation of adenylate cyclase. As ATP released from RBC is known to exert a vasodilator response, these results suggest a role for plasma ABA in the regulation of vascular ton

Journey on VX-809-Based Hybrid Derivatives towards Drug-like F508del-CFTR Correctors: From Molecular Modeling to Chemical Synthesis and Biological Assays

open12Cystic fibrosis (CF) is a genetic disease affecting the lungs and pancreas and causing progressive damage. CF is caused by mutations abolishing the function of CFTR, a protein whose role is chloride's mobilization in the epithelial cells of various organs. Recently a therapy focused on small molecules has been chosen as a main approach to contrast CF, designing and synthesizing compounds acting as misfolding (correctors) or defective channel gating (potentiators). Multi-drug therapies have been tested with different combinations of the two series of compounds. Previously, we designed and characterized two series of correctors, namely, hybrids, which were conceived including the aminoarylthiazole (AAT) core, merged with the benzodioxole carboxamide moiety featured by VX-809. In this paper, we herein proceeded with molecular modeling studies guiding the design of a new third series of hybrids, featuring structural variations at the thiazole moiety and modifications on position 4. These derivatives were tested in different assays including a YFP functional assay on models F508del-CFTR CFBE41o-cells, alone and in combination with VX-445, and by using electrophysiological techniques on human primary bronchial epithelia to demonstrate their F508del-CFTR corrector ability. This study is aimed (i) at identifying three molecules (9b, 9g, and 9j), useful as novel CFTR correctors with a good efficacy in rescuing the defect of F508del-CFTR; and (ii) at providing useful information to complete the structure-activity study within all the three series of hybrids as possible CFTR correctors, supporting the development of pharmacophore modelling studies, taking into account all the three series of hybrids. Finally, in silico evaluation of the hybrids pharmacokinetic (PK) properties contributed to highlight hybrid developability as drug-like correctors.openParodi, Alice; Righetti, Giada; Pesce, Emanuela; Salis, Annalisa; Tomati, Valeria; Pastorino, Cristina; Tasso, Bruno; Benvenuti, Mirko; Damonte, Gianluca; Pedemonte, Nicoletta; Cichero, Elena; Millo, EnricoParodi, Alice; Righetti, Giada; Pesce, Emanuela; Salis, Annalisa; Tomati, Valeria; Pastorino, Cristina; Tasso, Bruno; Benvenuti, Mirko; Damonte, Gianluca; Pedemonte, Nicoletta; Cichero, Elena; Millo, Enric

A New Generation of Hydrogen-Fueled Hybrid Propulsion Systems for the Urban Mobility of the Future

The H2-ICE project aims at developing, through numerical simulation, a new generation of hybrid powertrains featuring a hydrogen-fueled Internal Combustion Engine (ICE) suitable for 12 m urban buses in order to provide a reliable and cost-effective solution for the abatement of both CO2 and criteria pollutant emissions. The full exploitation of the potential of such a traction system requires a substantial enhancement of the state of the art since several issues have to be addressed. In particular, the choice of a more suitable fuel injection system and the control of the combustion process are extremely challenging. Firstly, a high-fidelity 3D-CFD model will be exploited to analyze the in-cylinder H2 fuel injection through supersonic flows. Then, after the optimization of the injection and combustion process, a 1D model of the whole engine system will be built and calibrated, allowing the identification of a “sweet spot” in the ultra-lean combustion region, characterized by extremely low NOx emissions and, at the same time, high combustion efficiencies. Moreover, to further enhance the engine efficiency well above 40%, different Waste Heat Recovery (WHR) systems will be carefully scrutinized, including both Organic Rankine Cycle (ORC)-based recovery units as well as electric turbo-compounding. A Selective Catalytic Reduction (SCR) aftertreatment system will be developed to further reduce NOx emissions to near-zero levels. Finally, a dedicated torque-based control strategy for the ICE coupled with the Energy Management Systems (EMSs) of the hybrid powertrain, both optimized by exploiting Vehicle-To-Everything (V2X) connection, allows targeting H2 consumption of 0.1 kg/km. Technologies developed in the H2-ICE project will enhance the know-how necessary to design and build engines and aftertreatment systems for the efficient exploitation of H2 as a fuel, as well as for their integration into hybrid powertrains

Identification of a high affinity binding site for abscisic acid on human lanthionine synthetase component C-like protein 2

Lanthionine synthetase component C-like protein 2 (LANCL2) has been identified as the mammalian receptor mediating the functional effects of the universal stress hormone abscisic acid (ABA) in mammals. ABA stimulates insulin independent glucose uptake in myocytes and adipocytes via LANCL2 binding in vitro, improves glucose tolerance in vivo and induces brown fat activity in vitro and in vivo. The emerging role of the ABA/LANCL2 system in glucose and lipid metabolism makes it an attractive target for pharmacological interventions in diabetes mellitus and the metabolic syndrome. The aim of this study was to investigate the presence of ABA binding site(s) on LANCL2 and identify the amino acid residues involved in ABA binding. Equilibrium binding assays ([3H]-ABA saturation binding and surface plasmon resonance analysis) suggested multiple ABA-binding sites, prompting us to perform a computational study that indicated one putative high-affinity and two low-affinity binding sites. Site-directed mutagenesis (single mutant R118I, triple mutants R118I/R22I/K362I and R118I/S41A/E46I) and equilibrium binding experiments on the mutated LANCL2 proteins identified a high-affinity ABA-binding site involving R118, with a KD of 2.6 nM ± 1.2 nM, as determined by surface plasmon resonance. Scatchard plot analysis of binding curves from both types of equilibrium binding assays revealed a Hill coefficient >1, suggesting cooperativity of ABA binding to LANCL2. Identification of the high-affinity ABA-binding site is expected to allow the design of ABA agonists/antagonists, which will help to understand the role of the ABA/LANCL2 system in human physiology and disease

AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma

AIRE is involved in susceptibility to melanoma perhaps regulating T cell immunity against melanoma antigens (MA). To address this issue, AIRE and MAGEB2 expressions were measured by real time PCR in medullary thymic epithelial cells (mTECs) from two strains of C57BL/6 mice bearing either T or C allelic variant of the rs1800522 AIRE SNP. Moreover, the extent of apoptosis induced by mTECs in MAGEB2-specific T cells and the susceptibility to in vivo melanoma B16F10 cell challenge were compared in the two mouse strains. The C allelic variant, protective in humans against melanoma, induced lower AIRE and MAGEB2 expression in C57BL/6 mouse mTECs than the T allele. Moreover, mTECs expressing the C allelic variant induced lower extent of apoptosis in MAGEB2-specific syngeneic T cells than mTECs bearing the T allelic variant (p < 0.05). Vaccination against MAGEB2 induced higher frequency of MAGEB2-specific CTL and exerted higher protective effect against melanoma development in mice bearing the CC AIRE genotype than in those bearing the TT one (p < 0.05). These findings show that allelic variants of one AIRE SNP may differentially shape the MA-specific T cell repertoire potentially influencing susceptibility to melanoma

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

How to Discriminate Between Leucine and Isoleucine by Low Energy ESI-TRAP MS(n)

In peptide sequencing experiments involving a single step tandem mass acquisition, leucine and isoleucine are indistinguishable because both are characterized by a 113 Da mass difference from the other peptide fragments in the MS2 spectrum. In this work, we propose a new method to distinguish between these two amino acids in consecutive MSn experiments, exploiting a gas-phase fragmentation of isoleucine that leads to a diagnostic 69 Da ion. We used this method to assess the Leu/Ile residues of several synthetic peptides. The procedure was then tested on a tryptic digest of myoglobin, assigning the correct amino acid in the majority of the peptides. This work was performed with an old and low-resolution instrument, thus demonstrating that our method is suitable for a wide number of ion trap mass spectrometers not necessarily expensive or up-to-date